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Dr. Pacenta takes us into the future of curing and treating pediatric cancer through the use of the patient's own immune system to target the cancer. At the forefront of the technology is CAR T-cell therapy targeting relapsed and refractory B-ALL cells to eradicate cancer with minimal side effects.
Dr. Holly Pacenta
Cook Children's Cellular Immunotherapy program
Cook Children’s Leukemia and Lymphoma care
Cook Children's Oncology program
Cook Children's Hematology and Oncology
Cook Children’s Hematology and Oncology Clinical Research
Host: Hello and welcome to Cook Children's Doc Talk. Our guest for this episode is pediatric hematologist oncologist Dr. Holly Pacenta. Dr. Pacenta began her career at Children's Hospital Colorado, where she developed her primary interest in new treatments for children with relapsed leukemia, including immunotherapy, cellular therapy and targeted therapy. She has been heavily involved in research, has published several works and received awards and recognition for her work. Today, Dr. Pacenta oversees the Cellular Immunotherapy program at Cook Children's where she and the oncology team are very excited about providing CAR T-cell therapy to patients with relapsed B-cell acute lymphoblastic leukemia, or ALL. Cellular immunotherapy introduces a new era in the treatment of children and young adults here at Cook Children's. Welcome Dr. Pacenta. We are very excited to have you here to talk about this incredible program and CAR T-cell therapy.
Dr. Pacenta: Thank you so much for having me.
Host: Can you start by giving us a little background on the cellular immunotherapy program and an overview of immunotherapy and CAR T-cell therapy?
Dr. Pacenta: Sure. So I think first to give an overview of immunotherapy and CAR T-cell therapy, we think at the forefront of the future of curing and treating pediatric cancer is to use, help use the patient's own immune system to target the cancer. So that's what immunotherapy is. Immuno meaning the immune system in therapy meeting treatments, so using the immune system to help treat your own cancer. And then CAR T-cell is a form, kind of a hybrid, of cellular immunotherapy. So we use one of the cells as part of the immune system, the T cells that typically help fight infection, and those get sent to a lab where they're reprogrammed to target the leukemia. So that's CAR T-cell therapy is. Then, our cellular immunotherapy program is a dedicated group of oncologists and stem cell transplant doctors here at Cook Children's along with some supportive services like pharmacy, dieticians, psychologists, etc., that will help provide these types of therapies to our patients.
Host: So KYMRIAH® is the CAR T-cell therapy currently approved for pediatric treatment of children and young adults with refractory or relapsed B-cell ALL, why this particular condition?
Dr. Pacenta: Immunotherapy and cellular therapy are a big interest in pediatric cancer in general. And there has been a lot of research to try to use this type of treatment for many different cancers. But the only one where it's currently approved is in B-cell ALL, which is the most common cancer we see in children. The reason why it's been successful in B ALL, is because this type of leukemia cells have specific markers that aren't located on many other cells in the body, which is the part about it that's a little bit unique. So it's been successful, because we're able to target this one marker on the leukemia cells and not have as much effect on the rest of the body.
Host: Chemotherapy and radiation therapy can be really, really harsh for kids with B-cell ALL, especially for those who have relapsed and can have long term effects. How does KYMRIAH differ from those treatments?
Dr. Pacenta: Chemotherapy and radiation therapy are more general and KYMRIAH or CAR T-cells are more focused therapy. So, like I had mentioned the CAR T-cells are really just attacking the leukemia cells themselves, they do have some effect on the healthy B-cells that have that same marker. But other than that they don't tend to affect the other cells in the body. So that means that while it does have some side effects, it has fewer than chemotherapy and radiation which affects all of the cells throughout the body. But one thing to point out is that chemotherapy and radiation therapy have been around for many, many years, and so. the long term side effects are better studied. As far as KYMRIAH, it wasn 't FDA approved until 2017. So while the short-term and long-term side effects seem like they are overall less, there are still a lot that we might not know about the long-term side effects and a treatment that's only been around for a couple of years.
Host: So we know that around 10 to 15% of patients don't respond to traditional treatment or relapse from traditional treatment methods, can you discuss how candidacy is determined for CAR T-cell therapy recipients and why CAR T-cell therapy is a treatment option?
Dr. Pacenta: CAR T-cell therapy is a treatment option for children with B-cell ALL who haven't responded the way that we've wanted to meaning that it's either refractory that it hasn't responded to the initial treatment or that it's relapse, meaning that it went away and then came back. So first of all, the patient has to meet that initial criteria of relapsed or refractory B-ALL and then they'll come to have a consultation with our cellular immunotherapy program, which includes me, and some other specialized doctors here at Cook Children's to help review the treatment and the process and determine that the patient and family are interested, and that this would be the best treatment for them.
Host:How does treatment with KYMRIAH work? Can you walk us through the treatment process?
Dr. Pacenta: So after the initial consultation, we'll have to set up a way for us to get the healthy T-cells from the child that we can use to send off to a lab and make into KYMRIAH or CAR T-cells. That involves setting up what we call leukapheresis, meaning that the patient comes to the hospital for one day, and they get connected through a bigger IV to a machine where its job is to separate the T-cells out from the blood, and then the blood gets circled back into the patient. Then, those T-cells are counted, and they're sent off to the laboratory at the drug company. And over a period of three to four weeks, some scientists will work on retargeting those cells to kill the leukemia. During that time, the child will be followed closely by our cellular immunotherapy team doctors to make sure that their leukemia stays well controlled and that they stay healthy, and that they don't develop any infections. At the end of those four weeks, approximately, when the CAR T-cells are ready, the patient will come back to Cook Children's for a four day short-course of chemotherapy. So they'll come and they'll get chemotherapy a few hours, and then they'll go home. The purpose of that chemotherapy is to help prep their body to accept the CAR T-cells. Then, on the day that we infuse the CAR T-cells, the medicine actually looks like any other medicine that we put through an IV, and we connect it up to the patient's IV and we watch the medicine or the cells drip into the patient. Typically, kids are able to go home after they receive the medicine on that day. And then we'll plan to follow them pretty closely in the clinic about twice a week to see if they develop any side effects.
Host:: So are each patient's cells then somewhat different? Is that why things have to be custom designed for each child?
Dr. Pacenta: So they're different in that the cells are from them, but the sort of process they do once they arrive at the lab is the same. So we're hoping that someday when we use it for other cancers, that instead of just targeting the leukemia cells, they'll be able to take it and target other things. But so far, they just target that one.
Host: There's hope that the T-cells will not only target current cancer cells, but help the patient's immune system recognize new cancer cells in the future preventing the cancer from returning long after treatment. What do we know so far? And when will we know how long the protection lasts?
Dr. Pacenta: So every patient is a little bit different. But we know that in some children that this can be a long-term cure, meaning that they don't need to receive any additional treatment. Some research studies have found that the CAR T-cells will persist in a patient's body for as long as three and a half years. But it's likely that the cells will be around for much longer. And we're still kind of waiting and doing research to find out really how long they'll last. I think as time passes, and as we continue to learn more about the cells, we'll have better ways to determine which patients are going to have long-term persistence of the cells and which patients might need additional treatment. But we haven't exactly figured all that out just yet.
Host: So are you planning to follow these patients over the long term?
Dr. Pacenta: Yeah.
Host: Kind of as a research as well as treating them as patients?
Dr. Pacenta: So the treatment that we have here at Cook Children's currently, is just the FDA approved treatment. So there are researchers at other hospitals that are kind of looking into more of the scientifics of how long the cells last. But after the patients receive their CAR T-cells, they'll continue to be followed by the cellular and immunotherapy team indefinitely. So there are some side effects. One of them is that since the CAR T-cells attack the B-cells, they kill the B-cells that are affected by the leukemia, but also the healthy B-cells. So these kids will need to continue to be followed by a specialist to make sure to minimize any risk of infection that they might have. And typically after the first month after they receive the CAR T-cells, they'll really just need to have monthly follow up.
Host: The great strides being made in treating pediatric ALL are very exciting. That said, there are so many other difficult to treat pediatric cancers Do you foresee a day when cellular therapy will replace chemo, surgery, or radiation therapy?
Dr. Pacenta: So I think there may be a day in the future when cellular therapy does replace chemo, surgery, and radiation for patients with cancer. But I do think that we're still a little ways off. This therapy has been very successful initially, but we still have a lot of work to do. First of all, it's difficult to tell which patients are going to be the ones that respond and which ones won't. So we're trying to do a little bit more research to try to figure that out to know which are the patients that are going to be cured for CAR T-cells. Then the other thing is that there are some patients that are cured with CAR T-cells, but the cure doesn't last. And so I think in the future, we may be able to develop a new or better CAR T-cell that's going to last forever. So hopefully someday, but we're not there yet.
Host: I keep thinking will there be like a cancer immunization?
Dr. Pacenta: That's that's the hope. Or maybe they're looking at some CAR T-cells that target multiple things. So maybe if they could individualize it more where for one person's cancer, they target three things for someone else's they target two, then it would be sort of more personalized and successful. We'll see.
Host: So for referring physicians which patients should they maybe contact our program to refer?
Dr. Pacenta: So any patient with B-cell ALL that's under the age of 25. That's the age group that we are currently trading here. In general, it's better to refer a patient earlier or at least have a conversation. Maybe they're not the best candidate right now. But they might be a better candidate in a few months. So in general, I would say any patient who has relapsed or refractory ALL, it'd be great to reach out, have a conversation. And then we can discuss if the patient's eligible. And if not now, then maybe at some point in the future, we could schedule a follow up.
Host: So you mentioned the age of 25, as kind of the cap, but what's the youngest that a patient could be potentially referred to us?
Dr. Pacenta: So I would say that there really is no youngest age that we're using to treat CAR T-cells. Patients are potentially eligible from the age of less than one up to 25. For the youngest kids, there can be a few more difficulties just because the babies are small, and we have to be able to collect a certain number of T-cells from their blood for the medicine to work. So it's really an individualized decision whether or not a smaller baby would be eligible, but it certainly is possible. And it's been done before.
Host: So what does the future look like then for immunotherapy trials and treatments here at Cook Children's?
Dr. Pacenta: We're working on fully establishing our program for the FDA approved form of CAR T-cells, which is known as KYMRIAH. But I think the future in our program is to work with other pediatric hospitals to try to open up clinical trials so that we can learn more about some of these things I was just describing. So we have some partnerships with other hospitals that we've worked with for other trials. And so I think within the next few years, we'll be planning to open clinical trials where either we'll be following kids getting the FDA approved KYMRIAH a little bit more closely, or we hope to open clinical trials where we'll be evaluating CAR T-cells for other cancers, or different types of CAR T-cells for B-cell ALL.
Host: This is such an exciting time not only for Cook Children's, but also our patients and their families. Thank you so much Dr. Pacenta for taking the time from your hectic schedule to talk about the cellular immunotherapy program and the important work that you're doing for hematology and oncology patients at Cook Children's as well as all across North Texas and the U.S. We look forward to seeing what's next.
Dr. Pacenta: Thank you so much for having me. So good to be here.
Host: We're so glad you could join us today. If you'd like to learn more about this program or any program at children's please visit us at Cook Children’s dot org.